The brain uses experience with environmental events to construct a framework for integrating the information received from its different senses. The end result is enhanced sensitivity to those cross-modal stimulus configurations that are likely to be derived from the same event. This capacity for 'multisensory integration' optimizes the brain's sensitivity to events of biological significance, and its behavioral responses to those events. It is of obvious survival value. The neural and behavioral manifestations of this process have been studied most extensively in the midbrain superior colliculus (SC), a structure involved in detecting and orienting to external stimuli. However, it is not yet known whether or not once formed during early life, the fundamental spatial and temporal principles that govern multisensory integration are 'fixed' thereafter, or can continue to adapt to changing environmental conditions. Nor is it known whether higher-order cognitive processes can co-opt these midbrain processes so that arbitrary covariant cross-modal features can be accommodated. Based on preliminary observations, we propose that the adult brain retains its sensitivity to the statistics of cross-modal events and is subject to cognitive oversight. Thus, any changes in those cross-modal statistics, or their significance, result in changes in the governing principles of multisensory integration. The present proposal uses multiple approaches and preparations to test these hypotheses. Adult animals will be exposed to systematic alterations in cross-modal statistics and/or their 'significance' via their association with reward. Then, the resultant short-term and long-term neural and behavioral effects of these experiences will be examined. The experiments are also designed to examine where in the neural circuit underlying SC multisensory integration, these experiences are encoded. PUBLIC HEALTH RELEVANCE: Anomalies in multisensory integration have been identified in a number of developmental disorders (e.g., Autism Spectrum Disorder, Dyslexia) and following various forms of traumatic and ischemic brain injury. Significant numbers of American families are negatively affected by these disorders, and while symptom-based multisensory rehabilitative strategies are now being used, our fundamental ignorance about the mechanisms of its inherent plasticity hampers innovation. Results of the proposed experiments will be of significant value in developing an empirical framework within which effective rehabilitative strategies can be developed.